ABSTRACT Due to their biological, social and economic vulnerabilities, adolescent girls and young women (AGYW) continue to be at increased risk for HIV acquisition. We propose an implementation research study to optimize woman-empowered HIV prevention strategies for AGYW. Key to optimizing HIV prevention strategies is an improved understanding of the multilevel determinants (individual, familial, relationship and community-level) of uptake and adherence to HIV prevention strategies targeting AGYW. Funded through a DREAMS Innovation grant, Witkoppen Health and Welfare Centre, a primary health clinic in Johannesburg, South Africa, will enroll HIV-negative AGYW unaware of the HIV status of their sexual partner(s) in an implementation research study. AGYW will be offered free home-based HIV self-testing for their male partners. Interested AGYW will be given HIV self-test kits and AGYW whose partners test HIV-positive or AGYW who remain unaware of their partner(s) HIV status will be offered pre-exposure prophylaxis (PrEP). The proposed work will build upon the DREAMS Innovation study described above. Using mixed methods, we will evaluate multi-level determinants of uptake and adherence to the novel AGYW-empowered HIV prevention strategy. Quantitative data collected by the DREAMS Innovation study will be complemented by the R21 with qualitative interviews with AGYW and their male partners at each of the steps of the proposed HIV prevention cascade: AGYW acceptance of self- testing kits for partners; AGYW delivery of self-testing kits to their male partner(s); male partner acceptance of HIV self-testing; disclosure of HIV test results to AGYW; linkage to care of HIV positive male partners; PrEP uptake among eligible AGYW; and PrEP adherence. Our specific aims are as follows: Aim 1: Understand the multi-level (individual, relationship and community) determinants of uptake and adherence to each of the steps of the novel AGYW-empowered HIV prevention strategy via a mixed methods approach. Combining data from the DREAMS Innovations Study and a community mapping study, we will use multi-level modeling to assess predictors of intervention uptake or adherence at each step of the HIV prevention cascade. At each step, we will also identify 6-8 AGYW and male partners (if relevant) who failed to complete the cascade step and perform qualitative interviews to explore reasons for not completing engagement in HIV prevention activities as well as facilitators of successful engagement in previous steps. Aim 2: Compare the effects of estimated HIV acquisition risk vs. perceived HIV risk on AGYW delivery of HIV self-tests to partners and PrEP uptake. We will estimate the proportion of intervention engagement explained by estimated HIV risk (per baseline risk assessments) vs. perceived HIV risk, examine the relationship between estimated and perceived risk, and describe changes in risk perception post-intervention.